Week 6.1 Lecture Slides On PCOS (PDF)

EHR522 EXERCISE FOR METABOLIC & RENAL CONDITIONS WEEK 6 – POLYCYSTIC OVARIAN SYNDROME (PCOS) POLYCYSTIC OVARIAN SYNDROME (PCOS) • Polycystic ovarian syndrome (PCOS) is an endocrinopathy of uncertain aetiology • Prevalence estimates vary based upon the diagnostic criteria used, but range from 4 – 2...

EHR522 EXERCISE FOR METABOLIC & RENAL CONDITIONS WEEK 6 – POLYCYSTIC OVARIAN SYNDROME (PCOS) POLYCYSTIC OVARIAN SYNDROME (PCOS) • Polycystic ovarian syndrome (PCOS) is an endocrinopathy of uncertain aetiology • Prevalence estimates vary based upon the diagnostic criteria used, but range from 4 – 20% of women of reproductive age • The many features of PCOS can be broadly divided into three categories - Clinical - Endocrine - Metabolic 2 PCOS – CLINICAL FEATURES Clinical features include − Menstrual abnormalities (oligomennorhea or amenorrhea) − Hirsutism − Acne − Alopecia − Anovulatory infertility − Recurrent miscarriages 3 PCOS – ENDOCRINE FEATURES • Endocrine features include elevated - Androgens - Luteinising hormone - Oestrogen - Prolactin 4 PCOS – METABOLIC FEATURES • Metabolic features often include - Insulin resistance - Obesity - Lipid abnormalities - Increased risk for impaired glucose tolerance and T2DM 5 PCOS – PREVALENCE OF COMMON FEATURES • Menstrual disturbances commonly observed in PCOS include oligomenorrhea, amenorrhea and prolonged erratic menstrual bleeding. However, 30% of women with PCOS have normal menses • Approximately 85 – 90% of women with oligomenorrhea have PCOS, while 30 – 40% of women with amenorrhea have PCOS • Infertility affects 40% of women with PCOS • Approximately 90 – 95% of anovulatory women presenting to infertility clinics have PCOS • Spontaneous abortion occurs more frequently in PCOS with incidence ranging from 42 – 73% 6 PCOS – RISK FACTORS • Risk factors for PCOS in adults include: - T1DM - T2DM - GDM 7 PCOS – COMMON COMORBIDITIES • Insulin resistance affects 50 – 70% of women with PCOS leading to a number of comorbidities, including - Metabolic syndrome - Hypertension - Dyslipidaemia - Glucose intolerance - Diabetes • Women with PCOS are more likely to have increased coronary artery calcium scores 8 PCOS – COMMON COMORBIDITIES • Mental health disorders occur more frequently in women with PCOS. These include - Depression - Anxiety - Bipolar disorder - Binge eating disorder 9 PCOS – DIAGNOSTIC CRITERIA • Controversy exists regarding the criteria used for PCOS diagnosis • Diagnosis of PCOS requires at least two of the following characteristics, in the absence of other causes, including pituitary and adrenal dysfunction - Clinical or biochemical hyperandrogenism - Anovulatory menstrual dysfunction - Polycystic ovaries on ultrasound 10 PCOS – DIAGNOSTIC CRITERIA • Although not included in the diagnostic criteria, insulin resistance, underpinned by insulin signalling pathway defects, is strongly implicated in the aetiology of PCOS • The polycystic ovary morphology is consistent with, but not essential for, the diagnosis of the syndrome 11 PCOS – PATHOPHYSIOLOGY • A complete explanation of the pathophysiology of PCOS is lacking. The heterogeneity of PCOS may in fact represent multiple pathophysiological mechanisms • Several theories have been proposed to explain the pathogenesis of PCOS - A unique defect in insulin action and secretion that leads to hyperinsulinaemia and insulin resistance - A primary neuroendocrine defect leading to an exaggerated luteinising hormone pulse frequency and amplitude - A defect of androgen synthesis that results in enhanced ovarian androgen production - An alteration in cortisol metabolism resulting in enhanced adrenal androgen production 12 PCOS – PATHOPHYSIOLOGY • A familial pattern in some cases suggests a genetic component, but the candidate genes are yet to be identified • There are links between PCOS and endometrial cancer, obesity, cardiovascular disease and diabetes mellitus with both short- and long-term consequences 13 PCOS – ECONOMIC BURDEN • PCOS costs the USA healthcare system $4.4 billion annually - 40% is attributed to treating reproductive dysfunction (infertility and menstrual dysfunction) - 40% is attributed to PCOS-related diabetes 14 PCOS – PHARMACEUTICAL INTERVENTION • Pharmaceutical treatment for PCOS focuses primarily on addressing reproductive dysfunction and insulin resistance • Oral contraceptives are used to treat menstrual irregularity, hirsutism and acne. Long-term use of oral contraceptives, however, remain controversial from a cardiometabolic standpoint • Spironolactone (aldosterone antagonist) and finasteride (5-alpha reductase inhibitor) are used to treat symptoms of androgen excess 15 PCOS – PHARMACEUTICAL INTERVENTION • Fertility treatments for PCOS include ovulation induction agents (such as Clomiphene Citrate) • Second-line fertility therapies include exogenous gonadotropins, laparoscopic ovarian drilling and assisted reproductive technology • Metformin is commonly used to improve insulin resistance, which can in turn play a role in ovulation induction • There is currently no ideal pharmacological intervention in PCOS and for this reason exercise, dietary modification and weight remain first-line management strategies to improve cardiovascular risk factors and reproductive dysfunction 16 PCOS – EXERCISE INTERVENTION • There are currently no evidence-based exercise guidelines for the treatment of PCOS • Exercise prescription should therefore be individualised to the patient based upon presentation and clinical features/comorbidities 17 PCOS – THE EVIDENCE FOR EXERCISE • Exercise intervention in women with PCOS has been shown to - Increase follicle-stimulating hormone - Increase sex hormone-binding globulin - Decrease total testosterone - Decrease androstenedione 18 PCOS – THE EVIDENCE FOR EXERCISE - WEIGHT • Due to a complex physiological interplay, many women with PCOS find it difficult to lose weight • Nonetheless, in women who do lose weight, the traditional exercise approach to the management of overweight and obese individuals is typically most successful 19 PCOS – THE EVIDENCE FOR EXERCISE – INSULIN RESISTANCE • Insulin resistance in PCOS is unique, being intrinsically present in the majority of lean PCOS women and further exacerbated by extrinsic obesity-related insulin resistance, however the mechanisms underlying insulin resistance are yet to be fully elucidated • Approximately half of the available studies in women with PCOS demonstrate an improvement in insulin resistance with an exercise intervention • PCOS patients with insulin resistance should be managed as you would manage a patient with pre-diabetes or T2DM managed through lifestyle approaches 20 PCOS – THE EVIDENCE FOR EXERCISE – BLOOD LIPIDS • The majority of the available studies in women with PCOS have not shown a reduction in blood lipids with exercise intervention • A limited number of studies however have demonstrated improvements in triglycerides, HDLc and LDLc with exercise intervention in women with PCOS 21 PCOS – THE EVIDENCE FOR EXERCISE – BLOOD PRESSURE • Approximately half of the available evidence suggests that exercise interventions in women with PCOS can reduce either systolic or diastolic blood pressure 22 PCOS – THE EVIDENCE FOR EXERCISE – REPRODUCTIVE FUNCTION • Of five available studies reporting on menstrual function in women with PCOS, three reported improvements in menstrual and/or ovulation frequency following exercise • The improvement in reproductive function was not dependent on the length of the intervention or the type of exercise performed • Exercise appears significantly more potent than dietary intervention in improving reproductive function in women with PCOS 23 PCOS – THE EVIDENCE FOR EXERCISE – SUMMARY • Despite the lack of well designed studies, lifestyle intervention, including exercise, is first-line therapy in the majority of women with PCOS • All studies that had successful outcomes with women with PCOS included moderate intensity supervised exercise (60 – 70% VO2max or HRR; 75 – 80% HR max) and reported improvements within 12 weeks of exercise, regardless of study duration • The most consistent improvements were demonstrated in - Weight loss - Insulin resistance - Reproductive function 24 PCOS – THE EVIDENCE FOR EXERCISE – SUMMARY • Insulin resistance underpins many of the clinical features and should therefore be a treatment target in PCOS • Enhanced insulin sensitivity underpins restoration of reproductive function through hormonal improvements, including reduced androgens 25 PCOS – THE EVIDENCE FOR EXERCISE – SUMMARY • Based on the results of the available studies, women with PCOS should be advised to engage in at least 90 minutes of aerobic activity per week at a moderate intensity to achieve improved reproductive and cardiometabolic outcomes • However, given the considerable variability in the design, intensity and outcome measures of the available studies, it is very difficult to make specific recommendations • Each patient should be treated as an individual with consideration being given to their presenting clinical features and comorbidities 26 WEEKLY READINGS Harrison, C. L., Lombard, C. B., Moran, L. J., & Teede, H. J. (2011). Exercise therapy in polycystic ovary syndrome: A systematic review. Human Reproduction Update, 17(2), 171-183. Sirmans, S. M., & Pate, K. A. (2013). Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clinical Epidemiology, 1-13. Tsilchorozidou, T., Overton, C., & Conway, G. S. (2004). The pathophysiology of polycystic ovary syndrome. Clinical Endocrinology, 60(1), 1-17. 27